Listening Fatigue & Speakers in Small Room

Replacing speaker is the right approach in this case. N804 aren't that big even for your small listening room, so you may search for similar but with less fatigue.
My thoughts would be towards Vandersteen 3A-sig or Aerial 7T

IMHO your problems stem from the fact that B&W speakers are not time-coherent (this is a huge discussion & there are Audiogon members who are dedicated to both sides of the fence. Search the archives here if you want to learn more) & it's a well-known fact that non time-coherent speakers create a lot of distortion that leads to many ill-effects, one of them being listening fatigue. No surprise here. You were lucky, I think, that you didn't experience this before. I used to own a DM604S2 long time back but my room is bigger. The N804s ar not much bigger than the DM604S2.
Yeah, the N804s might be too big for your room but before you run out & buy another different pair maybe you can experiment a little to see if you can alleviate your pain.

* Have you played with toe-in? Try zero toe-in where the speakers are pointing straight. Try toe-in such that the speakers fire at your directly i.e. remove reflected sound as much as you can.

* I see that you have treated the room which is very good. Maybe some more treatment is need? Maybe some on the ceiling to attenuate the reflected sound? Make sure that you have "spot panels" at the 1st reflection off the side walls.

* Make sure that you are sitting with your ears just below the tweeter & above the midrange. Atleast this was the best position for me when I had my DM604S2. You might want to start at this point & move up/down to see which is best for you. You might have to up/down your chair OR raise the speaker. I'm saying this because it very much looks to me that you are receiving a lot of high freq info & very little bass freq. So, the music is 'tipped up' which is worsening your listening fatigue. Changing your height will allow the drivers to integrate at your ear so your hear the whole audio spectrum.

* related to the above is to change your distance from the speaker. Maybe you are too close such that the drivers are not integrating at your ear so you are not hearing a cohesive sound - you might be hearing the tweeter & mid (as they do arrive before the bass) & very little/zero from the bass driver.
FWIW.

Actually, I thought to retube my preamp since the tubes had
been in use for several, and I mean SEVERAL years. I figured
that maybe they were weakening and causing more amplified
distortion from having to work harder than necessary. Well, it
appears to have worked. I listened for a couple of hours with
no fatigue at all. I will continue to monitor the situation,
but it seems like I will need to change out the tubes more
frequently, regardless. The quality of the sound is great with
new tubes, I just hope this has solved the fatigue problem.

Not to rain on your parade, but usually when small tubes grow old they loose some highs and become dullish. Usually.

On the other hand some new tubes are often dullish and take some hours to open up in the highs. So what you hear initially is not necessarily where you will end up after 24 hours.

I think Bombaywalla's comments are quite good and could be very helpful, especially those in the first and last recommendations. It is possible that if you are listening in the near field these speakers may not be appropriate, at least for the best results. Re toe in, don't omit trying some severe toe in where the speakers axis crosses well in front of your listening position. This can solve all kinds of issues including 1st reflection issues off the side walls and ceilings as well.

Lastly, tonally speaking, tube brands can make a very big difference.

I have experimented with toe in, and currently have them
firing straight ahead. However, I never tried extreme toe
in, so perhaps that's next. Also, there's no more room
behind me to sit, so I am maxed out in that regard.