Piratecat
Sesquipedalian
It hasn't come up. I think the answer is yes, and no. Massive localized pain can knock a person unconscious regardless of location; if you shatter my knee cap, I'm passing out from pain even though my head is unaffected.Would you allow Knockout to work on an enemy that was Huge/Gargantuan and also would you stipulate that the PC had to be able to hit the monster on the head?
I don't like taking away PC "toys" unless there's a darn good reason. Can you trip a gelatinous cube? Probably not, but you could conceivably set up vibrations that stop it from moving for a round, which has the same effect as tripping it. My default is to say "yes, but..." to players.
This sort of question came up last night when the PCs knocked a shapeless, flying monster "prone." I decided that in this case I was going to write a "can't be tripped or knocked prone" into their monster description. That's a better solution than making an ad hoc ruling that applies to all flying creatures.