I have noticed that when I fly without stopping to the 100+ level areas, enemies seem to stop spawning. But, when I fight my way at a slower pace killing things along the way, enemies continue to spawn. I'm assuming what is happening is that enemies spawn around me, then they get left behind, but take up space in some enemy spawn limit. So, if my guess is correct, what i'm suggesting is that non-important monsters (skeletons, pollywogs, klowns, etc., but not Ingot or the bosses, or the specific monsters in the evil cave or the cabin) that spawn randomly eventually despawn after some time outside of the player's render or view distance.
Again, all of this is based on a guess of what might be the cause of the problem.