Section 110.12(A) requires that unused and unintended openings (such as knockouts in enclosures that may have been knocked out by accident or for a raceway or cable that was never installed) must be put back together to restore the integrity of the enclosure. 

If the opening is intended for some purpose (perhaps drainage or mounting), then it is not required to be sealed up. The primary purpose of an enclosure is to protect electrical system from external influences, typically things like dirt and water, but also to protect from accidental contact and to exclude some things.