Biggest CDs are used at the start of the pull, usually they last long enough for everything to be dead. If the mobs can't be stunned then you have to pay a lot more attention to the tank's health, but if they can be stun locked then you can concentrate more on Holy spamming. Most tanks capable of speedrunning have a set rotation of big CDs to cycle through for each pull, but on the off chance they have nothing it's still safe to throw out 1 Holy or 2 (especially if the mobs can be stunned) but things may get dicey after that. Basically, Holy spam at the start with Regen + Med 2 ticks = safe in most situations.